Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with <i><scp>TP</scp>53</i> alterations

Lin, Richard J.; Ho, Caleb; Hilden, Patrick; Barker, Juliet N.; Giralt, Sergío; Hamlin, Paul A.; Jakubowski, Ann A.; Castro‐Malaspina, Hugo; Robinson, Kevin S.; Papadopoulos, Esperanza B.; Perales, Miguel-Ángel; Sauter, Craig S.

doi:10.1111/bjh.15721

Cited by 60 publications

(30 citation statements)

References 15 publications

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“…Allogenic SCT —This modality can be useful in high‐risk, transplant‐eligible TP53 ‐mutated relapsed MCL. Allo‐SCT can provide long term disease control in 30% of MCL patients …”

Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.

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“…Allogenic SCT —This modality can be useful in high‐risk, transplant‐eligible TP53 ‐mutated relapsed MCL. Allo‐SCT can provide long term disease control in 30% of MCL patients …”

Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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“…TP53 alterations were previously associated with a poor prognosis in MCL patients treated with standard treatment modalities 44,45 . A recent study suggested that allogeneic hematopoietic cell transplantation may be a beneficial treatment option for patients with TP53 mutations 46 . For the younger MCL patients receiving cytarabine-containing chemotherapy and autologous stem cell transplantation, Ferrero et al 9 developed the MIPI-genetic index (MIPI-g), which is a prognostic model integrating MIPI-c prognostic index with genetic data (TP53, and KMT2D mutations).…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study

Jeong

Park

Yun

et al. 2020

Sci Rep

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The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progressionfree survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes. Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin's lymphoma (NHL) accounting for 5-7% of all NHLs 1. Although MCL is uncommon (0.64/100,000 person-years), there has been a 130.9% rise in its incidence in recent years 2. Higher incidence rates have been seen in Caucasians (153.0%), Asians (96.

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“…[ 68 69 70 71 79 80 ] Young, physically fit patients with a Mantle Cell Lymphoma International Prognostic Index high-risk score with or without TP53 mutations or blastoid/pleomorphic variants can be considered for allogeneic SCT. [ 81 82 ] Finally, for patients unfit for treatment, oral corticosteroids and alkylating agents can be offered for symptom relief. Palliative radiotherapy can be offered to patients with compromised vital organs or for pain relief.…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

Saudi lymphoma group's clinical practice guidelines for diagnosis, management and follow-up of patients with various types of lymphoma during the Coronavirus Disease 2019 pandemic

Alzahrani¹,

Al-Mansour²,

Apostolidis³

et al. 2020

Saudi J Med Med Sci

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The Saudi Lymphoma Group had previously published recommendations on the management of the major subtypes of lymphoma. However, the effect the currently ongoing coronavirus disease 2019 (COVID-19) pandemic has on the management of patients with lymphoma has been paramount. Therefore, the Saudi Lymphoma Group has decided to provide clinical practice guidelines for the diagnosis, management and follow-up of patients with various types of lymphoma during the COVID-19 pandemic.

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Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations

Cited by 60 publications

References 15 publications

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study

Saudi lymphoma group's clinical practice guidelines for diagnosis, management and follow-up of patients with various types of lymphoma during the Coronavirus Disease 2019 pandemic

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